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Dynamics of mitochondrial DNA copy number regulation in relation to gastric cancer survival
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Dynamics of mitochondrial DNA copy number regulation in relation to gastric cancer survival
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Journal Article
Dynamics of mitochondrial DNA copy number regulation in relation to gastric cancer survival
2025
Overview
Purpose
To investigate the causal effects of gene expression levels associated with mitochondrial DNA copy number (mtDNA-CN) on cancer survival outcomes.
Methods
We performed two-sample mendelian randomization (MR) analyses to evaluate the causal relationship between mtDNA-CN in peripheral blood and overall survival period of different cancer types. Additionally, colocalization analyses were performed to identify genes whose expression correlates with mtDNA-CN. Furthermore, we investigated how expression levels of these genes impact survival period in different cancers.
Results
Higher mtDNA-CN in peripheral blood is significantly associated with reduced survival period in gastric cancer (HR = 72.97, 95% CI 68.86 to 77.08,
p
= 0.046). Colocalization analysis identified six genes,
PNP
,
CDK10
,
C7orf73
,
NLRP2
,
MYO15A
, and
OSGEP
, that regulate the mtDNA-CN in stomach tissue. Among them, higher expressions of
MYO15A
,
OSGEP
, and
CDK10
are significantly associated with shorter gastric cancer survival. Notably, the impact of
OSGEP
expression on survival was particularly significant in the
ERBB2
amplified subgroup (
p
= 0.025). Enrichment analysis suggests that the risk genes impact overall survival in gastric cancer prognosis by modulating mitochondrial function and DNA copy number.
Conclusion
Higher mtDNA-CN in peripheral is correlated with the shorter overall survival in gastric cancer patient. Higher expression of
MYO15A
,
OSGEP
, and
CDK10
is associated with shorter survival in gastric cancer patients, potentially by regulating mtDNA-CN, suggesting potential targets for future therapeutic interventions of gastric cancer.
Publisher
Springer US,Springer Nature B.V,Springer
Subject
